DNA mismatch repair-deficient non-neoplastic endometrial glands are common in Lynch syndrome patients and are present at a higher density than in the colon

Abstract

Aims: The hallmark of Lynch syndrome (LS) is DNA mismatch repair protein (MMR) deficiency. Recently, MMR deficiency in non-neoplastic colonic crypts has been identified as a novel indicator of LS. We aimed to determine whether MMR-deficient non-neoplastic endometrial glands can distinguish patients with and without LS, and to compare the level of MMR deficiency in the normal endometrium and colon in LS patients.

Methods and results: We evaluated the immunohistochemical expression of MMR proteins in the normal endometrial mucosa from 64 patients, including 34 patients with confirmed LS (17 with endometrial cancer and 17 without cancer), 30 patients with endometrial cancer without LS (10 with tumours with MLH1 promoter hypermethylation and 20 with MMR-proficient tumours), and in the normal colonic mucosa from 30 LS patients. MMR-deficient non-neoplastic endometrial glands were identified in 47% of LS patients and in no patients without LS (P < 0.001). MMR-deficient non-neoplastic glands were more often identified in LS patients with endometrial cancer (65%) than in those without endometrial cancer (29%) (P = 0.04). In contrast to what was seen in the normal colon, MMR-deficient glands in the normal endometrium were seen as large, contiguous groups, ranging in number from two to 101 (87% versus 45%, P = 0.02). MMR-deficient glands were identified at a higher density in the endometrium than in the colon in LS patients (median number of MMR-deficient glands, 22 versus two, P = 0.02).

Conclusions: Our findings indicate that MMR-deficient non-neoplastic endometrial glands constitute an indicator of LS, and that MMR-deficient glands in the endometrium are present in a pattern of contiguous large groups.

Keywords: DNA mismatch repair; colon; endometrium; immunohistochemistry; lynch syndrome.